The purpose of this project is to define the mechanism of regulation of the globin genes in erythroid cells. Control of globin mRNA metabolism is being studied by molecular hybridization analysis. Purified complementary DNAs specific for the individual globin mRNAs (beta for adult hemoglobin and gamma for fetal hemoglobin) are used to quantitate changes in the individual mRNAs during both normal ontogeny and experimental stress erythropoiesis. The molecular mechanism of erythropoietin is being analyzed by measurement of changes in beta A and beta C mRNAs during the erythropoietin induced switch from Hb A (alpha 2 beta A2) to Hb C (alpha 2 beta C2). Analysis of possible regulation at the DNA sequence level is being attempted by molecular cloning of the sheep globin genes. BIBLIOGRAPHIC REFERENCES: Benz, E.J., Jr., Geist, C., Steggles, A.W., Barker, J.E., and Nienhuis, A.W.: Hemoglobin switching in sheep and goats: VII. Preparation of complementary DNA's specific for the alpha, beta, and gamma globin messenger RNA's of sheep. J. Biol. Chem. 252: 1908-1977.